title: The β-ketoacyl-ACP synthase from Mycobacterium tuberculosis as potential drug targets.
abstract: The continuous preventive measures and control of tuberculosis are often hampered by re-emergence of multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis. A novel drug approach is desperately needed to combat the global threat posed by MDR strains. In spite of current advancement in biological techniques viz. microarray and proteomics data for tuberculosis, no such potent drug has been developed in the past decades yet. Therefore, mycolic acid is an essential constituent which is involved in the formation of cell wall of Mycobacterium species. The biosynthesis of mycolic acid is involved in two fatty acid synthase systems, the multifunctional polypeptide fatty acid synthase I (FASI) which performs de novo fatty acid synthesis and dissociate FASII system. FASII system consists of monofunctional enzymes and acyl carrier protein (ACP), elongating FASI products to long chain mycolic acid precursor. In this review, the β-ketoacyl-ACP synthases (fadH, kasA and kasB) are distinct and play a vital role in mycolic acid synthesis, cell wall synthesis, biofilm formation and also pathogenesis. On the basis of substantial observation we suggest that these enzymes may be used as promising and attractive targets for novel anti-TB drugs designing and discovery.
authors.affiliation: Epigenomics Project, Institute of Systems and Synthetic Biology, Universite d'Evry Val d'Essonne-Genopole-CNRS UPS3201, 5 rue Henri Desbrueres, 91030 Evry, France.
authors.forename: V
authors.initials: V
authors.lastname: Singh
authors.forename: I
authors.initials: I
authors.lastname: Mani
authors.forename: D K
authors.initials: DK
authors.lastname: Chaudhary
authors.forename: P
authors.initials: P
authors.lastname: Somvanshi
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005227:Fatty Acids / Q000096:biosynthesis; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D017434:Protein Structure, Tertiary; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D005227:Fatty Acids; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase